Production of stable quinine nanodispersions using esterified γ-polyglutamic acid biopolymer

Novel methods are needed for the development of nanodispersed drug formulations to enhance bioavailability of many hydrophobic pharmaceuticals. The poorly water-soluble quinine is a well-known anti-malaria drug which can be used as a promising model compound for the development of novel nanodispersed formulations. In addition to hydrophobic drug's own affecting properties, surfactants play an important role for the enhancement of their low bioavailability by preparing stable dispersions. Amphiphilic compounds can efficiently be used to stabilize colloidal fragments by preventing the precipitation or crystallization of poorly water-soluble active ingredients during fabrication. A novel biopolymer derivative based on the biotechnologically produced gamma-polyglutamic acid (gamma-PGA) from Bacillus licheniformis cultivation was developed for encapsulation of the active ingredient. High-molecular gamma-PGA is an anionic polyelectrolyte that was optimized and modified with hydrophobic L-phenylalanine ethyl ester (L-PAE) to form an amphiphilic comb polymer P(gamma-GA-r-L-PAE) with surfactive properties. The approach of the nanodispersion polymer concentration, molecular weight and grafting degree enables the efficient stabilization of the poorly water-soluble model drug. The research presented in this report indicates the potential benefits of hydrophobically modified gamma-PGA and suggests its potential role in forming stable dispersions for future pharmaceutical applications. (C) 2013 Elsevier B.V. All rights reserved.